Reporting that the combination treatment has a “manageable safety profile”, the investigators believe their findings “support the favourable benefit–risk profile of this regimen and offer a new potential option for patients with heavily pretreated metastatic breast cancer.”

Median PFS was determined by independent radiology review to be 8.44 months for the 270 patients who were randomly assigned to receive 21-day cycles of chemotherapy consisting of utidelone 30 mg/m2 per day on days 1–15 plus capecitabine 1000 mg/m2 twice daily on days 1–14.

This compared with a median PFS of 4.27 months for the 135 patients using capecitabine only, giving a significant hazard ratio (HR) of 0.46.

Peripheral neuropathy was the most common grade 3 adverse effect in patients given utidelone plus capecitabine, affecting 22%. Noting that the patients had all previously used taxanes and other agents associated with peripheral neuropathy, the team hypothesizes that “[t]hese previous regimens could have sensitised patients to utidelone-induced peripheral neuropathy.”

Palmar–plantar erythrodysaesthesia was the most common grade 3 event common in patients given capecitabine alone (8%) and the third most common grade 3 event for those given combination treatment (7%), after neutropenia (12%).

There were sixteen serious adverse events in the combination treatment arm and 14 in the capecitabine only arm, with diarrhoea reported in three and two patients, respectively.

Further analysis indicated that patients given combination treatment were significantly more likely to have an objective response than those treated with capecitabine monotherapy (40.4 vs 21.5%) and to derive clinical benefit from treatment (53.9 vs 26.0%), defined as a complete or partial response or stable disease for at least 6 months.

The trial investigators explain in The Lancet Oncology that overall survival (OS) data are immature but that at cutoff utidelone plus capecitabine appeared to offer longer OS, at a median of 16.13 months versus 12.78 months with capecitabine monotherapy, and a significant HR of 0.63.

However, Xavier Pivot, from University Hospital J Minjoz in Besançon, France, cautions in an accompanying article that “[a]lthough encouraging, mature overall survival data are needed before making any decision for regulatory approval of utidelone.”

He also notes that a quarter of the patients in the trial had HER2-positive breast cancer and that subsequent targeted treatment may affect the final OS analysis.

“In the future, large randomised studies in metastatic breast cancer should include a statistical plan that is able to provide conclusions about overall survival and the population should be restricted to a group of patients that unquestionably require chemotherapy alone”, the commentator recommends.